Liang-Ge-San inhibits dengue virus serotype 2 infection by reducing caveolin1-induced cytoplasmic heat shock protein 70 translocation into the plasma membrane.

BACKGROUND: Dengue virus (DENV) is a major public health threat. However, there are no specific therapeutic drugs for DENV. Many Chinese heat-cleaning formulas, such as Liang-Ge-San (LGS), have been frequently used in the virus-induced diseases. The antiviral effect of LGS has not been reported yet. PURPOSE: In this study, the effect of LGS on the inhibition of dengue virus serotype 2 (DENV-2) was investigated and the relevant mechanism was explored. METHODS: High-performance liquid chromatography was applied to analyze the chemical characterization of LGS. The in vitro antiviral activities of LGS against DENV-2 were evaluated by time-of-drug-addition assay. The binding of heat shock protein 70 (Hsp70) and envelope (E) protein or caveolin1 (Cav1) were analyzed by immunofluorescence and immunoprecipitation assays. Then the role of Cav1 in the anti-DENV-2 effects of LGS was further examined. DENV-2 infected Institute of Cancer Research suckling mice (n = 10) and AG129 mice (n = 8) were used to examine the protective effects of LGS. RESULTS: It was found that geniposide, liquiritin, forsythenside A, forsythin, baicalin, baicalein, rhein, and emodin maybe the characteristic components of LGS. LGS inhibited the early stage of DENV-2 infection, decreased the expression levels of viral E and non-structural protein 1 (NS1) proteins. LGS also reduced E protein and Hsp70 binding and attenuated the translocation of Hsp70 from cytoplasm to the cell membrane. Moreover, LGS decreased the binding of Hsp70 to Cav1. Further study showed that the overexpression of Cav1 reversed LGS-mediated E protein and Hsp70 inhibition in the plasma membrane. In the in vivo study, LGS was highly effective in prolonging the survival time, reducing viral loads. CONCLUSION: This work demonstrates for the first time that LGS exerts anti-DENV-2 activity in vitro and in vivo. LGS decreases DENV-2-stimulated cytoplasmic Hsp70 translocation into the plasma membrane by Cav1 inhibition, thereby inhibiting the early stage of virus infection. These findings indicate that LGS may be a candidate for the treatment of DENV.

Esophagus two-step-cut overlap method in esophagojejunostomy after laparoscopic gastrectomy.

PURPOSE: Esophagojejunostomy is a challenging step in laparoscopic gastrectomy. Although the overlap method is a safe and feasible approach for esophagojejunostomy, it has several technical limitations. We developed novel modifications for the overlap method to overcome these disadvantages. METHODS: Forty-eight consecutive gastric cancer patients underwent totally laparoscopic total gastrectomy or laparoscopic proximal gastrectomy with double-tract reconstruction at our institution from January 2019 to April 2020 using the overlap method with the following modifications. The esophagus was initially rotated by 90° counterclockwise, followed by transection of two-thirds of the esophageal diameter. The unstapled esophagus was then transected with a harmonic ultrasonic scalpel to enable esophagostomy at the posterior side of the esophagus. A side-to-side esophagojejunostomy was then formed at the posterior side of the esophagus using an endoscopic linear stapler through the right lower trocar. The common entry hole was closed via hand sewing method using V-Loc suture. This procedure was termed "esophagus two-step-cut overlap method." RESULTS: Only one patient suffered from esophagojejunal anastomotic leakage but subsequently recovered after conservative treatment. Patients did not experience anastomotic bleeding or stricture. CONCLUSION: Our modified overlap method provides satisfactory surgical outcomes and overcomes several technical limitations, such as entering the false lumen of the esophagus, unnecessary pollution caused by nasogastric tube, and unintended left crus stapling during anastomosis.

Port-site metastasis of unsuspected gallbladder carcinoma with ossification after laparoscopic cholecystectomy: A case report.

BACKGROUND: Unsuspected gallbladder carcinoma (UGC) refers to cholecystectomy due to benign gallbladder disease, which is pathologically confirmed as gallbladder cancer during or after surgery. Port-site metastasis (PSM) of UGC following laparoscopic cholecystectomy is rare, especially after several years. CASE SUMMARY: A 55-year-old man presenting with acute cholecystitis and gallstones was treated by laparoscopic cholecystectomy in July 2008. Histological analysis revealed unexpected papillary adenocarcinoma of the gallbladder with gallstones, which indicated that the tumor had spread to the muscular space (pT1b). Radical resection of gallbladder carcinoma was performed 10 d later. In January 2018, the patient was admitted to our hospital for a mass in the upper abdominal wall after surgery for gallbladder cancer 10 years ago. Laparoscopic exploration and complete resection of the abdominal wall tumor were successfully performed. Pathological diagnosis showed metastatic or invasive, moderately differentiated adenocarcinoma in fibrous tissue with massive ossification. Immuno-histochemistry and medical history were consistent with invasion or metastasis of gallbladder carcinoma. His general condition was well at follow-up of 31 mo. No recurrence was found by ultrasound and epigastric enhanced computed tomography. CONCLUSION: PSM of gallbladder cancer is often accompanied by peritoneal metastasis, which indicates poor prognosis. Once PSM occurs after surgery, laparoscopic exploration is recommended to rule out abdominal metastasis to avoid unnecessary surgery.

[Effects of Shengmai Jianghuang San on intestinal flora in nude mice with radio resistant cells of nasopharyngeal carcinoma].

Modern pharmacological studies have shown that Shengmai San has the effects of enhancing immunity and improving blood circulation, and Curcumae Longae Rhizoma(Jianghuang) has anti-inflammatory, anti-cancer, anti-oxidation and other functions. Shengmai San combined with Jianghuang is a new research direction in the study of anti-tumor of traditional Chinese medicines. The main treatment for nasopharyngeal carcinoma is radiation therapy, but radiation therapy can cause a variety of side effects, and it also changes the composition of the intestinal flora. In this study, the 16 s rDNA sequencing platform was used to perform macro-sequence sequencing of the intestinal flora samples of nude mice bearing the veins of Shengmai Jianghuang San, and then the results of intestinal flora data were analyzed to investigate the effect of Shengmai Jianghuang San on tumors. The results showed that Shengmai Jianghuang San combined with irradiation could enhance the therapeutic effect of tumor treatment. Radiation therapy would reduce the total number and diversity of intestinal flora in nude mice, and also change the structure of the flora. Shengmai Jianghuang San could protect the diversity of colonies, and also partially restore the colony imbalance caused by irradiation. This study provides a research idea for Shengmai Jianghuang San as a sensitizing adjuvant for radiotherapy of nasopharyngeal carcinoma.